ABSTRACT: The clinical translation of various immunologic strategies to elicit antitumor responses in the cancer patient has been disappointing. Active specific immunotherapies in the form of vaccines have been able to elicit cellular responses to tumor-associated antigens, but have been insufficient in causing tumor regression in patients with metastatic disease. To date, one of the more promising therapies is the adoptive transfer of immunoreactive T cells as documented in clinical trials. This approach appears to be more effective in patients who are pre-conditioned to be lymphodepleted with chemotherapy. Our laboratory has been interested in developing methods in animal models to preferentially activate and expand tumor reactive T cells obtained from tumor-draining lymph nodes (TDLN) or vaccine-primed lymph nodes. These methodologies have been used in several clinical trials of adoptive immunotherapy. During this past funding period, we identified that activated B cells derived from TDLN possess antitumor reactivity that can mediate tumor regression in adoptive immunotherapy. Investigating the interactions of tumor-primed T and B cells during in vitro activation, and in vivo after adoptive transfer form the basis of the proposed studies in this project. The specific aims are: 1. Evaluate tumor-primed B cells as antitumor effector cells 2. Evaluate the mechanisms by which B cells mediate antitumor effects 3. Examine mechanisms involved in enhanced tumor reactivity of adoptively transferred B effector cells in the lymphodepleted host 4. Examine the potential immune suppression between T cells and B cell subsets in adoptive immunotherapy We hypothesize that tumor-primed B cells can collaborate with effector T cells in adoptive cellular therapies of cancer.